title: Sarcoglycans and integrins in bisphosphonate treatment: immunohistochemical and scanning electron microscopy study.
abstract: Osteonecrosis of the jaw is an adverse outcome associated with bisphosphonate treatment. Bisphosphonates are used in conjunction with antineoplastic chemotherapy for the treatment of hypercalcaemia associated with malignancy, lytic bone metastasis and multiple myeloma. However, it is not known if the osteonecrosis of the jaw lesion originates in the bone or whether it initiates in the gingival epithelium. Two bisphosphonates are commonly used in cancer treatment. One of these is pamidronate disodium, a second-generation bisphosphonate that differs from the first-generation drug because it inhibits bone resorption at a dose that does not affect bone mineralization. The other widely used BP, zoledronate, is a third-generation drug that is the most potent bisphosphonate in clinical use, showing strong anti-osteoclastic activity, similar to pamidronate. The aim of the present study was to evaluate the modifications of human oral mucosa and underlying bone in patients after treatment with these nitrogen-containing bisphosphonates for 24 and 36 months. We analyzed the structural damage of the oral mucosa and damage of the perilesional mandibular bone observing possible correlations from them. Our results allow to express two hypotheses about the mechanism responsible for these results relating to mandible matrix necrosis; first, an increased skeletal microdamage associated with turnover suppression occurred early in treatment and progress with longer treatment duration, second, opening damage in osteonecrosis of the jaw modifies structural morphology of gingival epithelium.
authors.affiliation: Department of Experimental Medical, Surgical and Odontostomatological Sciences, University of Messina, Messina, Italy.
authors.forename: Francesco Saverio
authors.initials: FS
authors.lastname: De Ponte
authors.forename: Angelo
authors.initials: A
authors.lastname: Favaloro
authors.forename: Enrico Nastro
authors.initials: EN
authors.lastname: Siniscalchi
authors.forename: Antonio
authors.initials: A
authors.lastname: Centofanti
authors.forename: Michele
authors.initials: M
authors.lastname: Runci
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Cutroneo
authors.forename: Luciano
authors.initials: L
authors.lastname: Catalfamo
mesh_terms: D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D001862:Bone Resorption / Q000188:drug therapy / Q000235:genetics; D002113:Calcification, Physiologic / Q000187:drug effects; D002448:Cell Adhesion / Q000235:genetics*; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects; D064420:Drug-Related Side Effects and Adverse Reactions / Q000473:pathology; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects; D007150:Immunohistochemistry; D016023:Integrins / Q000096:biosynthesis* / Q000235:genetics; D007568:Jaw / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D009061:Mouth Mucosa / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D010020:Osteonecrosis / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology; D000077268:Pamidronate; D049031:Sarcoglycans / Q000096:biosynthesis* / Q000235:genetics; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D016023:Integrins; D049031:Sarcoglycans; D000077211:Zoledronic Acid; D000077268:Pamidronate